A 12-month, Open Label, Randomised, Effectiveness Study to Evaluate Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) Inhalation Powder Delivered Once Daily Via a Novel Dry Powder Inhaler (NDPI) Compared With the Existing COPD Maintenance Therapy Alone in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 3
- Intervention
- FF/VI
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 2802
- Locations
- 1
- Primary Endpoint
- Mean Annual Rate of Moderate or Severe COPD Exacerbations
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study is designed to compare the effectiveness and safety of Fluticasone Furoate/Vilanterol Inhalation Powder (100mcg Fluticasone Furoate ((FF), GW685698)/25mcg Vilanterol ((VI), GW642444)) delivered once daily via a Novel Dry Powder Inhaler (NDPI) compared with the existing COPD maintenance therapy over twelve months in subjects diagnosed with COPD. This is a Phase III multi-centre, randomised open label study. Subjects who meet the eligibility criteria are randomised and will enter a 12 month treatment period.
Detailed Description
This is a Phase III multi-centre, randomised open label study performed in subjects followed in primary care who have a diagnosis of and receive regular treatment for COPD in a localised geographical region of the UK
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects eligible for enrolment in the study must meet all of the following criteria:
- •Type of subject: Subjects with documented GP diagnosis of COPD, and currently receiving maintenance therapy
- •Informed consent: Subjects must be able to provide informed consent, have their consent signed and dated. Subjects must be able to complete the electronic subject questionnaires or allow a proxy to do so on their behalf.
- •Gender and Age: Male or female subjects aged ≥40 years of age at Visit 1 A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However in questionable cases, a blood sample with FSH \> 40MIU/ml and estradiol \<40pg/ml (\<140 pmol/L) is confirmatory. Or child bearing potential has a negative urine pregnancy test at Visit 2, and agrees to one of the highly effective and acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - Visit 2 to the end of the study).
- •Subjects with Exacerbation History
- •Current COPD Maintenance Therapy
Exclusion Criteria
- •Subjects meeting any of the following criteria must not be enrolled in the study:
- •Subjects with any life threatening condition (e.g. low probability (in the opinion of the GP/Investigator) of 12 month survival due to severity of COPD or co-morbid condition) at the point of entry into the study.
- •Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the GP/ Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- •Subjects with unstable COPD, defined as the occurrence of the following in the 2 weeks prior to Visit 2:
- •Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.
- •Chronic user of oral corticosteroids: Subjects who, in the opinion of the GP/Investigator, are considered to be a chronic user of oral corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening)
- •Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g., beta-agonists, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the GP/ Investigator, contraindicates the subject's participation will also be excluded.
- •Investigational Medications: A subject must not have used any investigational drug treatment within 30 days prior to Visit 2 or within five half-lives (t½) of the prior investigational study (whichever is the longer of the two).
- •Subjects who plan to move away from the geographical area where the study is being conducted during the study period and/or if subjects have not consented to their medical records being part of the electronic medical records database that is operational in the Salford area.
Arms & Interventions
FF/VI
once daily via a Novel Dry Powder Inhaler
Intervention: FF/VI
Existing Maintenance Therapy
Existing Maintenance Therapy: * Long acting bronchodilator therapy alone * ICS alone or in combination with a long acting bronchodilator * Triple maintenance therapy
Intervention: Existing Maintenance Therapy
Outcomes
Primary Outcomes
Mean Annual Rate of Moderate or Severe COPD Exacerbations
Time Frame: Up to 54 weeks
Mean annual rate of moderate or severe COPD exacerbations during treatment were assessed. Moderate exacerbation: participant received exacerbation-related prescription of oral corticosteroids and/ or antibiotic (with/without National Health Service \[NHS\] contact) not requiring hospitalisation. Severe exacerbation: an exacerbation-related hospitalisation. Analysis method was Generalised Linear Model (GLM) assuming the negative binomial distribution with a log-link function and logarithm of time on treatment as an offset variable, adjusted for randomized treatment, baseline COPD maintenance therapy per randomisation stratification, number of moderate/severe COPD exacerbations in previous year and smoking status at baseline. Intent to treat (ITT) population: all randomised participants who received a prescription of study medication. Primary Efficacy Analysis Population: all ITT participants who had at least one moderate/severe exacerbation in the year prior to randomization
Secondary Outcomes
- Number of COPD-related Primary Care Contacts Expressed Using Least Square Mean(Up to 54 weeks)
- Number of Participants With Non-serious Adverse Drug Reactions (ADR)(Up to 54 weeks)
- Number of Participants With Serious Adverse Events (SAEs) of Pneumonia During the Study(Up to 58 weeks)
- Number of All Secondary Care Contacts Expressed Using Least Square Mean(Up to 54 weeks)
- Number of All Primary Care Contacts Expressed Using Least Square Mean(Up to 54 weeks)
- Time to an Event of Discontinuation of Initial Therapy Occurring in a Year(Up to 364 days)
- Number of COPD-related Secondary Care Contacts Expressed as Least Square Mean(Up to 54 weeks)
- Number of Participants With Serious Adverse Events(Up to 56 weeks)
- Number of Participants With Serious Adverse Drug Reactions(Upto 12 months)
- Mean Number of Serious Adverse Events of Pneumonia During the Study(Up to 58 weeks)
- Time to the First Serious Adverse Event of Pneumonia Occuring in a Year(Up to 52 weeks)
- Time to the Addition of a Further COPD Controller Medication Occurring in a Year(Up to 364 days)
- Time to First Moderate/Severe Exacerbations Occurring in a Year(Up to 364 days)
- Time to First Moderate/Severe Exacerbations on Initial Therapy Occurring in a Year(Up to 364 days)
- Time to First Severe Exacerbations Occurring in a Year(Up to 364 days)
- Number of Participants With Fatal Serious Adverse Events of Pneumonia(Upto 58 weeks)